Tablet formulations of pharmaceutically active drugs are not normally comprised purely of the active ingredient. Excipient materials are usually included in tablet formulations to confer the necessary and desirable characteristics of a pharmaceutically acceptable tablet (e.g., acceptable hardness, rate of dissolution, and stability and a size and weight practical for oral administration). For example, diluents increase bulk, binders impart cohesive qualities, lubricants prevent adhesion to the surface of dies and punches during tableting operations, glidants improve flow characteristics, disintegrating agents facilitate breakup or disintegration after administration, coloring agents improve aesthetics and flavoring agents enhance palatability.
Directly-compressible drug compositions are prepared by a variety of techniques. Of the commonly employed methods, wet-granulation is the most widely used. The wet-granulation method is employed with formulations that are difficult to tablet and requires complicated steps of powder-mixing, kneading, granulation, drying, sieving and mixing.
More specifically, in wet-granulation a mixture of powdered active pharmaceutical and excipients is granulated by adding or spraying a binder solution until a wet mass is formed. The wet mass is dried, milled and then blended with a lubricant to form a directly-compressible pharmaceutical composition. This process is complicated, time-consuming, and costly.
In some instances, spray drying techniques are useful in preparing directly-compressible drug compositions. In a spray drying operation an aqueous mixture of the ingredients is atomized and passed into a chamber through which hot drying gas is circulated. The solvent rapidly evaporates and porous, uniform granules comprised of evenly distributed ingredients are recovered (e.g., see "Spray Drying Handbook" by K. Masters, Fourth Edition, Longmans/Wiley, New York, 1985).
Compositions containing spray-dried drug components can exhibit increased lubricity (e.g., see U.S. Pat. No. 4,904,477) or produce less friable tablets (e.g., see Canadian Patent 1 168 156). In some instances, spray-dried drug compositions are directly compressible into acceptable tablets (e.g., see U.S. Pat. No. 4,710,519).
Directly-compressible naproxen and naproxen sodium compositions are prepared by a wet-granulation method. Naproxen or naproxen sodium is obtained from synthesis as a wet cake or an aqueous mixture (e.g., see U.S. Pat. Nos. 4,723,033; 4,605,758; 4,246,164; and 4,009,197). The wet naproxen or naproxen sodium is dried. The dry drug is milled and then is blended with the disintegrating agent. To the dry blend is added a solution of binder to form a wet-granulation mixture of active ingredient, disintegrating agent and binder. The wet mixture is dried and milled to form a dry naproxen or naproxen sodium composition which is blended with lubricant and additional disintegrating agent to form a directly-compressible naproxen or naproxen sodium composition.
The drying and milling steps necessary in the wet-granulation of naproxen or naproxen sodium are costly in terms of energy, labor and capital equipment. A considerable advantage is realized if spray-drying techniques can be employed to eliminate such steps. However, directly-compressible compositions are not readily prepared from spray-dried naproxen or naproxen sodium compositions. Compositions comprising spray-dried naproxen or naproxen sodium may exhibit poor compressibility and compactibility characteristics or the tablets prepared therefrom may have poor dissolution characteristics.
The disclosure of these and other documents referred to throughout this application (e.g., in the Detailed Description of the Invention) are incorporated herein by reference.